title: Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis.
abstract: Matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) play a key role in the pathogenesis of multiple sclerosis (MS) and have been proposed as biomarkers of response to therapy. We investigated serum levels of several MMPs and TIMPs in 43 relapsing-remitting MS (RRMS) patients undergoing interferon-beta (IFN-b) treatment and classified as responders and non-responders based on clinical criteria. Levels of MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA before treatment and after 3, 6, 12, and 24 months of therapy. Neutralizing antibodies were determined by the myxovirus A induction bioassay. Treatment with IFN-b induced changes in levels of MMP-9 and TIMP-1. In contrast to non-responders, IFN-b resulted in an early and sustained increase in TIMP-1 levels in MS patients who showed clinical response to IFN-b. The early and sustained increase in TIMP-1 levels could be a marker of the response to IFN-b during the first 2 years of treatment.
authors.affiliation: Unitat de Neuroimmunologia Clínica, CEM-Cat, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain. mcomabel@ir.vhebron.net
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.forename: Jordi
authors.initials: J
authors.lastname: Río
authors.forename: Carmen
authors.initials: C
authors.lastname: Espejo
authors.forename: Mamen
authors.initials: M
authors.lastname: Ruiz de Villa
authors.forename: Hammad
authors.initials: H
authors.lastname: Al-Zayat
authors.forename: Carlos
authors.initials: C
authors.lastname: Nos
authors.forename: Florian
authors.initials: F
authors.lastname: Deisenhammer
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
authors.forename: Lara
authors.initials: L
authors.lastname: Nonell
authors.forename: Cristina
authors.initials: C
authors.lastname: López
authors.forename: Eva
authors.initials: E
authors.lastname: Julià
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D007155:Immunologic Factors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D016899:Interferon-beta; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9